RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA
M. PHARM SYNOPSIS
YEAR OF ADMISSION-JUNE 2009
TITLE OF THE SYNOPSIS
FORMULATION AND EVALUATION OF TIZANIDINE HYDROCHLORIDE TRANSDERMAL PATCHES
BY
PRAVEEN M
M. PHARM., PART-I
DEPARTMENT OF PHARMACEUTICS
UNDER THE GUIDANCE OF
Mr. B. SOMESWARA RAO, M. Pharm.
Associate Professor
DEPARTMENT OF PHARMACEUTICS
INSTITUTION
SREE SIDDAGANGA COLLEGE OF PHARMACY
B. H. ROAD, TUMKUR-572 102
KARNATAKA
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES BANGALORE, KARNATAKA
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / NAME OF THE CANDIDATEAND ADDRESS / PRAVEEN M.
S/o MANJANNA
SONDEKOPPA POST
BANGALORE NORTH TALUK ,
BANGALORE URBAN DISTRICT-562 130
2. / NAME OF THE INSTITUTION / SREE SIDDAGANGA COLLEGE OF PHARMACY
B. H. ROAD, TUMKUR- 572 102
KARNATAKA
3. / COURSE OF STUDY AND SUBJECT / MASTER OF PHARMACY IN PHARMACEUTICS
4. / DATE OF ADMISSION OF COURSE / JUNE- 2009
5. TITLE OF THE TOPIC
“FORMULATION AND EVALUATION OF TIZANIDINE HYDROCHLORIDE TRANSDERMAL PATCHES”
6.0 / BRIEF REVIEW OF THE INTENDED WORK
6.1 - Need for the study
A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a time-released dose of medication through the skin for treating systemic illnesses.1 The transdermal route of administration is recognized as one of the potential route for local and systemic delivery of drugs, it also provides a controlled release of medicament into patients.2
Transdermal delivery has many advantages over conventional modes of drug administration.
Ø It avoids hepatic first pass metabolism.
Ø Potentially decreases side effects.3
Ø Additionally, transdermal administration, as compared to other routes, is fairly noninvasive, patients are quite willing to accept the use of a simple looking patch as it can be conveniently applied and removed.4
Tizanidine, an imidazoline derivative, is α2-adrenergic agonist and centrally acting myotonolytic skeletal muscle relaxant with a structure unrelated to other muscle relaxants. It reduces spasticity by increasing presynaptic inhibition of motor neurons and also reduces increased muscle tone associated with spasticity in patients with multiple sclerosis or spinal cord injury.5 The oral administration of tizanidine has poor bioavailability due to its extreme hepatic first pass metabolism and also has low therapeutic drug concentration. The transdermal route maintains the plasma drug level for a longer period of time. The tizanidine solubility studies and apparent partition coefficient shows the suitable drug for transdermal delivery. The physicochemical and pharmacokinetic parameters of tizanidine suggests that it is an ideal drug canditate for transdermal drug delivery.6
The aim of present study is to formulate and evaluate tizanidine hydrochloride transdermal patches.
6.2 - Review of Literature
1. Development and evaluation of carvedilol transdermal patches, in this study transdermal patches of carvedilol were formulated using the hydrophilic polymer matrix of hydroxy propyl methyl cellulose (HPMC) in order to achieve controlled release of the drug, the prepared patches were characterized for physiochemical properties, invitro permeation profile across excised hairless guinea pig skin and skin irritation studies in albino rabbits.7
2. Design and invitro evaluation of haloperidol lactate transdermal patches containing ethyl cellulose-povidone as film polymers. Various physiochemical parameters such as solubility studies, partition coefficient, flux, enhancement ratio and dissolution studies of the formulated films were performed. The prepared films were subjected to Scanning Electron Microscopy (SEM), and Fourier Transform Infrared spectroscopy (FT-IR) spectra analysis. The results indicate that the formulation was found to be best for sustained release once a day formulation.8
3. Pharmacodynamics of ampicillin sodium transdermal patches in an invitro infection model. This study was to examine the activity of ampicillin sodium transdermal patches using different kinds of polymers such as sodium alginate, cellulose acetate phthalate, HPMC, chitosan and carboxy methyl cellulose studied through colony-forming units (CFU). It was found that against Escherichia coli the drug releasing capacity of HPMC was the best polymer followed by carboxy methyl cellulose, chitosan, cellulose acetate phthalate and sodium alginate.9
4. Nanoemulsions as vehicle for transdermal delivery of aceclofenac. The study investigated the potential of nanoemulsion formulation for transdermal delivery of aceclofenac and the prepared nanoemulsion were subjected to different thermodynamic stability studies like droplet size, refractive index and viscosity. The invitro skin permeation profile of this formulation was compared with conventional dosage form, the results suggested that nanoemulsions are potential vehicles for improved transdermal delivery of aceclofenac.10
5. Physiochemical and pharmacokinetic parameters in drug selection and loading for transdermal drug delivery, the ideal properties for selection of a drug candidate for transdermal drug delivery, the factors to be considered for transdermal dose calculation are reported.11
6. Design and evaluation of matrix type and membrane controlled transdermal delivery systems of nicotine, suitable for use in smoking cessation, invitro release studies of transdermal patches were discussed.12
7. Microemulsion as a vehicle for transdermal permeation of nimesulide. Topical microemulsions of nimesulide, a poorly water soluble nonsteroidal anti-inflammatory dug using olive oil as oil phase and tween 80 as surfactant. Various concentrations of surfactant, co-surfactants were used in constructing a pseudoternary phase diagram. Invitro permeation study of the gel was carried out through excised hairless rat skin and compared with a marketed preparation.13
8. Preparation of transdermal monolithic systems of indapamide by solvent casting method and the use of vegetable oil as permeation enhancer. In this transdermal monolithic systems of indapamide were prepared by using HPMC and ethyl cellulose polymers. The invitro studies shows that HPMC containing films have better release than that of ethyl cellulose containing films without any permeation enhancer.14
9. A novel metered dose transdermal spray formulation for oxybutynin. In this oxybutynin release from a series of ethanol/acetone/methylal based formulaton was assessed to various physicochemical parameters studies, diffusion studies, and skin irritation studies. It suggests that oxybutynin was the best metered dose transdermal spray formulation.15
6.3 - Objective of the Study
To formulate and evaluate tizanidine hydrochloride transdermal patches using different polymers.
7.0 / MATERIALS AND METHODS
Materials:
Drug : Tizanidine hydrochloride
Polymers : Hydroxy Propyl Methyl Cellulose, Methyl Cellulose,
Poly Vinyl Alcohol, Poly Vinyl Pyrollidine, etc.
Diffusion cell : Franz diffusion cell / Modified Franz diffusion cell.
Reagents : The reagents, solvents and other excipients of analytical grade.
Methods:
Solvent casting technique / standard procedure to be followed.
7.1 - Source of Data
Review of Literature from
a) Journals such as,
1) Indian Journal of Pharmaceutical Sciences
2) European Journal of Pharmaceutical Sciences
3) International Journal of Pharmaceuticals
4) Drug Delivery
5) Drug Development & Industrial Pharmacy
6) Journal of Pharmaceutical and Biomedical Analysis
b) World Wide Web
c) J-gate@Helinet
d) Library: Sree Siddaganga College of Pharmacy
e) E-library: Sree Siddaganga College of Pharmacy
7.2 - Method of collection of data
A] Development of transdermal drug delivery system
B] Pre-formulation study such as
Solubility
Partition coefficient
Calibration
Compatibility of drugs with polymers
C] Characterization study
Uniformity of weight
Tensile strength
Folding endurance
Percentage moisture absorption
Percentage moisture loss
Water vapour transmission rate
Drug content
Invitro diffusion study
Skin irritation test on Rabbits
Stability study
/ 7.3 - Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, please describe briefly.
YES- Skin irritation test of prepared transdermal patches will be carried out on
Rabbits.
7.4 - Has ethical clearance been obtained from your institution in case of 7.3?
Approval number:71/2009-10, dtd.30-11-09.Copy enclosed.
8.0 / REFERENCES
1. Zhao JH, Fu JH, Wang SM, Su CH, Shan Y, Kong SJ et al. A novel transdermal patch incorporating isosorbide dinitrate with bisoprolol: in vitro and in vivo characterization. Int J Pharm 2007;337:88-101.
2. Ramesh G, Vamshi VY, Kishan V, Madhusan RY. Development of nitrendipine transdermal patches. Curr Drug Deliv 2007;4:69-76.
3. Das MK, Bhattacharya A, Ghoshal SK. Transdermal delivery of trazodone hydrochloride from acrylic films prepared from aqueous latex. Indian J Pharm Sci 2006;68:41-6.
4. Troy DB, editor. Remington: The Science and Practice of Pharmacy,vol I, 21st ed. Noida:B.I.Publications Pvt. Ltd.2005. p. 948.
5. Mahadik KR, Paradkar AR, Agrawal H, Kaul N. Stability –indicating HPTLC determination of tizanidine hydrochloride in bulk drug and pharmaceutical formulations. J Pharmaceut Biomed Anal 2003;33:545-52.
6. Mutalik S, Parekh HS, Nigel M, Davies NM, Udupa N. A combined approach of chemical enhancers and sonophorosis for the transdermal delivery of tizanidine hydrochloride. Drug Deliv 2009;16:82-91.
7. Yuveraj ST, Chetan SC, Anusha S. Development and evaluation of
carvedilol transdermal patches. Acta Pharm 2007;57:151-9.
8. Sadashivaiah R, Dinesh BM, Uma AP, Desai BG, Raghu KS. Design and
invitro evaluation of haloperidol lactate transdermal patches. Asian J Pharm
2008;43-9.
9. Bagyalakshmi J, Williams AS, Mithun AW, Ravi TK, Manavalan R, Manna PK. Pharmacodynamics of ampicillin sodium transdermal patches in an in vitro infection model. Indian J Pharm Sci 2006;68:540-1.
10. Shakeel F, Sanjula B, Ahuja A, Javed A, Aqil M, Shafiq S. Nanoemulsions as
vehicles for transdermal delivery of aceclofenac. AAPS PharmSciTech
2007;8:107.
11. Chandrashekar NS, Shoba Rani RH, Physicochemical and Pharmacokinetic parameters in drug selection. Indian J Pharm Sci 2008;70:94-6.
12. Shaila L, Pandey S, Udupa N. Design and evaluation of matrix type and membrane controlled transdermal delivery system of nicotine suitable for use in smoking cessation Indian J Pharm Sci 2006;179-83.
13. Derle DV, Sagar BHS, Rohini P. Microemulsion as a vehicle for transdermal permeation of nimesulide. Indian J Pharm Sci 2006;68:622-5.
14. Sanap GS, Dama GY, Hande AS, Karpe SP, Nalawade SV, Kakade RS. Preparation of transdermal monolithic systems of indapamide by solvent casting method and use of vegetable oil as permeation enhancer. Int Green Pharm 2008;129-33.
15. Bhakshi A, Bajaj A, Malhotra G, Madan M, Amrutiya N. A novel metered dose transdermal spray formulation for oxybutinyn. Indian J Pharm Sci 2008;70:733-9.
9.0 /
SIGNATURE OF THE CANDIDATE
10. / REMARKS OF THE GUIDE / Recommended
11. / NAME AND DESIGNATION OF
11.1 Guide / Mr. SOMESWARA RAO B. M. Pharm.
Associate professor
Department of Pharmaceutics
11.2 Signature
11.3 Co-Guide ( If any)
11.4 Signature
11.5 Head of the Department / Dr. SURESH KULAKARNI, M. Pharm., Ph. D
Professor & Head
Department of Pharmaceutics
11.6 Signature
12. / 12.1 Remark of the Principal / Forwarded to the University for approval
12.2 Signature
/
(Dr. S. Badami)
PrincipalSree Siddaganga College of Pharmacy
B. H. Road, Tumkur-572 102
10